Scorpion venom component III inhibits cell proliferation by modulating NF-κB activation in human leukemia cells

Abstract

Abstract. Scorpion venom contains various groups of compounds that exhibit anticancer activity against a variety of malignancies through a poorly understood mechanism. While the aberrant activation of nuclear factor κB (NF-κB) has been linked with hematopoietic malignancies, we hypothesized that scorpion venom mediates its effects by modulating the NF-κB signaling pathway. In the present study, we examined the effects of scorpion venom component III (SVCIII) on the human leukemia cell lines THP-1 and Jurkat and focused on the NF-κB signaling pathway. Our results showed that SVCIII inhibited cell proliferation, caused cell cycle arrest at G1 phase and inhibited the expression of cell cycle regulatory protein cyclin D1 in a dose-dependent manner in THP-1 and Jurkat cells. SVCIII also suppressed the constitutive NF-κB activation through inhibition of the phosphorylation and degradation of IκBα. NF-κB luciferase reporter activity was also inhibited by SVCIII. Our data suggest that SVCIII, a natural compound, may exert its antiproliferative effects by inhibiting the activation of NF-κB and, thus, has potential use in the treatment of hematopoietic malignancies, alone or in combination with other agents.

Purificación parcial de péptidos y actividad citotóxica del veneno T. macrochirus

“…Con base en los resultados descritos, es posible concluir que el componente peptídico del veneno de T. macrochirus tuvo actividad citotóxica en las líneas celulares evaluadas, lo cual se ha observado también en péptidos purificados y sintetizados a partir de otros venenos de escorpión, por lo cual se han empezado a considerar como una alternativa para el diseño y la elaboración de nuevos agentes terapéuticos (13,16,18,(43)(44)(45)(46)(47)(48)(49)(50)(51). De ahí la necesidad de separar completamente algunos de los péptidos de este veneno y evaluar el efecto que cada uno de ellos produce en las diferentes líneas celulares evaluadas para determinar plenamente el responsable de cada uno de los efectos observados.…”

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

“…Fu, Jiao, Zheng, Liang, and Hu (2014) transfected the plasmid pEGFP‐N1‐BmK (4.0 μg of DNA), containing the BmK CT gene (isolated from B. martensii Karsch) into rat glioma C6 cells. Subsequently, the therapeutic agent LiCl (50 mM), which inhibits migration and invasion in glioma cells, was added as a co‐treatment, obtaining 75% cytotoxicity within 24 h. Song et al (2012) purified SVIII toxin from B. martensii Karsch venom and investigated its anticancer potential against the THP‐1 (acute monocytic leukemia) and Jurkat cell lines (acute T cell leukemia), obtaining 66.6% (IC 50 value: 50 μg/mL) and 58.7% (IC 50 value: 50 μg/mL) of cytotoxicity, respectively. Similarly, Zhao, Qiao, Zhang, and Shao (2010) utilized I‐BmK CT fraction against the C6 cell line, and showed a mortality rate of 60.5% with an IC 50 value of 2.0 mg/mL.…”

“…B. martensii arrested the cell cycle in the G1 and S phases (Li, Li, Zhao, Yuan, & Mao, 2014), while H. bengalensis arrested the cell cycle in the sub‐G1 phase (Gupta et al, 2007). rAGAP and scorpion venom component III (SVCIII) induced cellular arrest in G1 phase (Gu et al, 2012; Song et al, 2012). On the other hand, Bengalin and Cn2 arrested the cell cycle in sub‐G1 and G0/G1 phases, respectively (Escalona et al, 2014; Gupta et al, 2010) (Table 3).…”

In vitro determination of the efficacy of scorpion venoms as anti-cancer agents against colorectal cancer cells: a nano-liposomal delivery approach

“…In a recent study, it has been reported that the scorpion venom restricted cell progression, caused by the cell cycle arrest at the G0/G1 phase, and restricted the production of cell cycle regulatory protein cyclin D1 in in vitro human leukemia cells. 39 The venom also suppressed the constitutive NF-κB activation through restriction of the phosphorylation and breakdown of IκBα. 39 Taken together, the findings such as low cell survival, higher ROS and apoptosis, and cell cycle arrest strongly suggest the anti-cancer potential of scorpion venoms used in this study.…”

“…39 The venom also suppressed the constitutive NF-κB activation through restriction of the phosphorylation and breakdown of IκBα. 39 Taken together, the findings such as low cell survival, higher ROS and apoptosis, and cell cycle arrest strongly suggest the anti-cancer potential of scorpion venoms used in this study. This study further suggests that the venom efficiency increased multifold when utilized in the encapsulated form.…”